Mice that are heterozygous for the targeted mutation are viable and fertile. There is a reduced viability (9%) prior to weaning for homozygous offspring from heterozygous parents. Surviving homozygous mice display delayed growth and motor dysfunctions. No gene product (mRNA) is detected by Northern blot analysis in homozygous ES cells. In situ hybridization reveals no detectable expression in hippocampal neurons and Purkinje cells of heterozygotes with a maternal deficiency. Due to imprinting, with preferential expression of the maternal allele, heterozygous mice with a maternal deficiency display the phenotype while heterozygous mice with a paternal deficiency do not. Heterozygous mice with the maternal deficiency display reduced motor coordination, impaired long-term potentiation, and context-dependent learning abnormalities. Homozygous mice and heterozygous mice with a maternal deficiency have increased Purkinje cell cytoplasmic levels of TRP53, transformation related protein 53, an...
Dr. Arthur Beaudet, Baylor College of Medicine
Mice that are heterozygous for the targeted mutation are viable and fertile. There is a reduced viability (9%) prior to weaning for homozygous offspring from heterozygous parents. Surviving homozygous mice display delayed growth and motor dysfunctions. No gene product (mRNA) is detected by Northern blot analysis in homozygous ES cells. In situ hybridization reveals no detectable expression in hippocampal neurons and Purkinje cells of heterozygotes with a maternal deficiency. Due to imprinting, with preferential expression of the maternal allele, heterozygous mice with a maternal deficiency display the phenotype while heterozygous mice with a paternal deficiency do not. Heterozygous mice with the maternal deficiency display reduced motor coordination, impaired long-term potentiation, and context-dependent learning abnormalities. Homozygous mice and heterozygous mice with a maternal deficiency have increased Purkinje cell cytoplasmic levels of TRP53, transformation related protein 53, and an increased susceptibility to tonic clonic seizures induced by handling. This mutant mouse strain represents a model that may be useful in studies of Angelman syndrome.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes and a loxP site was used to disrupt a 3 kb sequence including exon 2. The construct was electroporated into 129S7 /SvEvBrd-Hprtb-m2 derived AB2.2 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.
|Allele Name||targeted mutation 1, Arthur L Beaudet|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||E6-AP-; E6AP-; Ube3A KO|
|Gene Symbol and Name||Ube3a, ubiquitin protein ligase E3A|
|Gene Synonym(s)||5830462N02Rik; 5830462N02Rik; A130086L21Rik; A130086L21Rik; ANCR; AS; E6-AP; E6-AP ubiquitin protein ligase; EPVE6AP; HPVE6A; Hpve6a; RIKEN cDNA 5830462N02 gene; RIKEN cDNA A130086L21 gene|
|Strain of Origin||129S7/SvEvBrd-Hprt |
|Molecular Note||A 3kb genomic region including exon 2 was replaced with a neo-loxP-hprt cassette via homologous recombination, resulting in deletion of 100 N-terminal amino acids in the encoded protein and a frameshift inactivating all putative protein isoforms. Homozygous mutant animals were identified by Southern blot and PCR genotype analysis.|
|Mutations Made By|| |
Dr. Arthur Beaudet, Baylor College of Medicine
The resulting chimeric animals were crossed to 129 mice. The strain is maintained as a heterozygote due to variable homozygous lethality. Expected coat color is: Agouti.
|Please inquire about possible genotypes.|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of
each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders
are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in
order to provide the minimum number of animals, animals will ship within 25 weeks.
The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.